Robust Circadian Oscillations in Growing Cyanobacteria Require Transcriptional Feedback

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Science  10 May 2013:
Vol. 340, Issue 6133, pp. 737-740
DOI: 10.1126/science.1230996

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Keeping in Synch

Although it differs from mammalian clocks, the circadian clock of cyanobacteria is a valuable model for understanding how such clocks function. At the heart of the cyanobacterial clock is a posttranslational regulation (PTR) circuit in which the phosphorylation of the clock protein KaiC oscillates. This circuit is apparently sufficient for generating rhythms, but it is connected to a transcriptional-translational (TTR) feedback loop more similar to the one that functions in mammals. This TTR loop is, at least in some conditions, dispensable. To understand the role of the TTR circuit, Teng et al. (p. 737) engineered cyanobacteria so that the circadian behavior of individual cells in a population of growing cells could be monitored. Cells engineered to lack the TTR mechanism had rhythmic clocks but fell out of synch with the other cells in a population over time. The experimental results together with mathematical modeling indicate that the TTR mechanism is important to allow cells to robustly stay in rhythm with one another in the absence of synchronizing external cues.


The remarkably stable circadian oscillations of single cyanobacteria enable a population of growing cells to maintain synchrony for weeks. The cyanobacterial pacemaker is a posttranslational regulation (PTR) circuit that generates circadian oscillations in the phosphorylation state of the clock protein KaiC. Layered on top of the PTR is transcriptional-translational feedback regulation (TTR), common to all circadian systems, consisting of a negative feedback loop in which KaiC regulates its own production. We found that the PTR circuit is sufficient to generate oscillations in growing cyanobacteria. However, in the absence of TTR, individual oscillators were less stable and synchrony was not maintained in a population of cells. Experimentally constrained mathematical modeling reproduced sustained oscillations in the PTR circuit alone and demonstrated the importance of TTR for oscillator synchrony.

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